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General Pharmacology 2 > Antimicrobial Therapy: Intro > Flashcards

Antimicrobial Therapy: Intro Flashcards

1
Q

Antimicrobial Minimum Inhibitory Concentration

A
  • Minimum inhibitory Concentration (MIC)
  • Lowest concentration of antimicrobial needed to inhibit visible microbial growth
  • Estimates susceptibility of specific bacteria to antimicrobials
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2
Q

MIC results

A
  • Reported as:
    • Susceptible: reasonable likelihood of success
    • Intermediate: increases in dose may result in success or highly susceptible location in body
    • Resistant: unlikely to result in clinical success
  • Factors affecting susceptibility breakpoints
    • animal species
    • Bacteria
    • Disease
    • Drug
    • Dose
    • Route
    • Frequency
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3
Q

Spectrum

A

The bacteria typically susceptible to an antimicrobial

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4
Q

Resistance:

Intrinsic

A

the bacteria were never susceptible to the antimicrobial

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5
Q

Resistance:

Acquired

A

at some point the bacteria were susceptible to the antimicrobial

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6
Q

Resistance

A
  • We do NOT “cause” resistant mechanisms, we select for them
  • The mechanisms are already often in the bacterial population or occur through spontaneous mutation independent of antimicrobial treatment
    • when susceptible die off, the resistant strains are left and flourish
  • Mechanisms of resistnace include:
    • efflux pumps or decreased uptake
    • inactivation of the antibiotic
    • modify the target
  • Resistance mechanisms may be shared within bacterial species or between bacterial species
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7
Q

Treatment Goals:

Therapeutic

A

clear the infection

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8
Q

Treathment Goals:

Prophylaxis / Prevention

A

Treating prior to bacterial exposure to prevent infection

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9
Q

Treatment Goals:

Growth Promotion

A

feeding antimicrobials decreases subclinical disease or alters microbiome resulting in more efficient feed conversions

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10
Q

Treatment Goal:

Do we need to treat?

A
  • is there a benefit to treatment?
  • Is there even an infection?
  • A fever may not be due to an infection. It could be inflammation, hyperthermia
  • Avoid/minimize adverse effects
  • Avoid bacterial resistance selection
  • Avoid violative residues in food animals
  • Ensure client compliance
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11
Q

Bactericidal

A

antimicrobial kills bacteria

beta lactams, aminoglycosides, nirtoimidazoles, fluoroquinolones

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12
Q

Bacteriostatic

A

inhibit microbial growth

Tetracyclines, macrolides / lincosamides, sulfonamides, -phenicols

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13
Q

Pharmacodynamics - What is our target?

Peak / concentration dependent (CMAX:MIC)

A
  • fluroquinolones, aminoglycosides, metronidazole
  • Rate/extent of killing increase with increasing concnetrations, then plateaus at about 10X MIC
  • Post-antibiotic Effect (PAE):
    • continued bacterial death / inhibition due to bacterial damage
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14
Q

Pharmacodynamics - What is our target?

Time above MIC (T>MIC)

A
  • Beta Lactams, sulfas, -phenicols
  • More important to maintain concentrations above MIC, but no major advantage to markedly exceeeding the MIC
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15
Q

Pharmacodynamics - What is our target?

AUC:MIC

A
  • Tetracyclines, macrolides/lincosamides, fluorquinolones
  • Total drug exposure over time
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16
Q

Pharmacokinetics - effect of dividing a total daily dose

A
  • CMAX higher for once daily administration
    • CMAX = 140 mcg/ml given every 24 hours
    • CMAX = 70 mcg/ml given every 12 hours
    • Important for concentration dependent
    • Not so important for time dependent
  • CMIN is lowe for once daily administration
    • CMIN = 0.05 mcg/ml given every 24 hours
    • CMIN = 1.5 mcg/ml given every 12 hours
    • More dificult to maintian T > MIC
    • Drug free interval decreases aminoglycoside renal toxicity
  • AUC
    • typically the same for either dosage
17
Q

Routes of Administration:

Oral

A
  • “Ease” of administration, typical lower cost, may increase GI adverse effects
  • Fluoroquinolones, Macrolides / lincosamides, metronidazole, TMs
  • Some: Beta lactams, -phenicols, tetracyclines
18
Q

Routes of Administration:

Parenteral (IV, IM, SQ)

A
  • May provide more consistent and higher concentrations than PO
  • May increase client compliance
  • Route for drugs with low bioavailability
    • poor lipophilicity
    • First pass metabolism
    • Unstable in GIT
  • Aminoglycosides, also same FQs, macrolides, -phenicols, tetracyclines
19
Q

Routes of Administration:

Topical

A
  • Higher concentrations at site of infection
    • may enhance spectrum
  • Less systemic adverse effects
  • Drugs that are toxic systemically, may be applied topically
20
Q

Routes of Elimination:

Metabolism

A

Hypically inactivates Macrolides, -phenicols

21
Q

Routes of Elimination:

Biliary Secretion

A

may be active drug or inactive metabolite

Doxycycline

22
Q

Routes of Elimination:

Renal Elimination

A

May result in high concentrations in the urine and increase efficacy for UTIs

Beta-lactams, aminoglycosides, trimethoprim, some tetracyclines, some fluoroquinolones

23
Q

Drug penetration into protected tissues

A

CNS, prostate, eye, bronchi

  • Limitaitons include:
    • lipophilicity
    • protein binding
    • efflux transporters
  • In general:
    • fluoroquinolones
    • -phenicols
    • Trimethoprim / sulfonamide
    • Some macrolides
    • Some tetracyclines
    • Some cephalosporins penetrate CNS/Prostate/Eye/ well
      • cephalexin
24
Q

Species Differences:

Horses

A

Many antimicrobials disrupt GIT flora, resulting in overgrwoth of pathogenic/opportunistic bacteria = sepsis and death

Many antimicrobials also have poor oral bioavailability

Conversely IV doxycycline is lethal, but can be administered PO

25
Q

Species Differences:

cattle

A

Drug residues, compliance, resistance

26
Q

Species Differences:

Dogs

A

Sulfonamides - autoimmune like reactions, KCS

27
Q

Species Differences:

Cats

A

Fluoroquinolone retinal degeneration

Doxycycline, clindamycin esophageal stricture

28
Q

Banned Drugs (Food Animal)

A
  • Extralabel use prohibited:
    • chloramphenicol - no label
    • Nitroimidazoles - no label
    • Fluoroquinolones
    • Nitrofurazones - no label
    • Glycopeptides - some label use
    • Sulfonamides in lactating dairy cows over 20 months of age
    • Cephalosporins - extralabel doses/routes prohibited, but therapeutic applications in unlaneled diseases OK
      • applies to major species
      • Minor species ELDU allowed, cephapirin intrammamary is an exception
29
Q

Limitations of use:

Treatment Failure?

A
  • Misdiagnosis
  • incorrect dose / route / frequency
  • Immunosuppression
  • Compliance
  • Underlying disease
  • Foreign body / implant / nidus
  • Pharmacokinetic interaction
  • True antimicrobial resistance
  • Reinfection vs. Failure
30
Q

Limitations of Use:

Abscesses

A

antimicrobials are unlikely to be effective without drainage

Inability to penetrate and remain active at necessary concentrations

31
Q

Limitations of use:

Pseudomonas spp.

A
  • Most Pseudomonas are difficult to treat. If possible use topical
    • PO effectively limited to Fluoroquinolones
    • Ceftazidime, carbapenems, anti-pseudomonal penicillins, aminoglycosides
32
Q

Limitations of Use:

Enterococcus spp.

A
  • Amoxicillin >>> Tetracylines, chloramphenicols, rifampin, fluoroquinolones, nitrofurantoin
  • Regardless of susceptibility testing, chephalosporins, trimethoprim sulfa, clindamycin, aminoglycosides, azithromycin are ineffective
  • If resistant and a co-infection with Enterococcus, sometimes treating the other pathogens will result in clearance of Enterococcus spp.

General Pharmacology 2 (17 decks)

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